The Th1, Th2, and Th17 paradigm in inflammatory bowel disease

Abstract

Effectiveness of monoclonal antibody against TNF-α as a treatment for both Crohn's disease (CD) and ulcerative colitis (UC) changed the natural history of inflammatory bowel disease (IBD), and this subsequently encouraged many scientists to develop more effective therapies targeting other cytokine pathways. CD4+T cells play central roles for the formation of cytokine networks in the pathogenesis of IBD. When CD4+T cells are developed in the thymus and migrate to the peripheral tissues, they are called naïve T cells, which secrete little cytokines and cannot exert efficient effector function. When antigens specific for their own T-cell receptors (TCR) are presented to naïve T cells by antigen-presenting cells (APC) through MHC class-II/TCR signals with co-stimulatory signals, naïve T cells differentiate to helper T cells, which secrete characteristic types of cytokines and express specific transcription factors. Cytokines in the environment where antigen presentation occurs determine the polarization of these helper T (Th) cell subgroups. Classic helper T cells have been classified as Th1 or Th2. Th17, which is a novel subset of effector T cells, and regulatory T cells (Treg), which regulate effector T cells negatively, have taken part in them recently. In the past, CD was thought to be Th1-mediated disease, while UC was thought to be Th2-mediated disease. However, recently, it has been reported that Th17 are deeply involved in the pathogenesis of multiple animal models of IBD that were thought to be Th1 or Th2 models, and actually Th17 cytokines are highly expressed in the intestinal mucosa of both CD and UC patients. In addition, according to the results of GWAS (Genome Wide Association Study), there are highly significant associations between genomic regions of Th17/IL-23 pathway and IBD. This section will be helpful for the understanding of future immunologic therapies for IBD, which seems to become more and more complex.